High-Dose Melatonin Shows Promise in Improving Outcomes for Critically Ill COVID-19 Patients
A recent study conducted at Hospital Clínico San Carlos in Madrid, Spain, suggests that high doses of oral melatonin may significantly improve clinical outcomes and reduce mortality in critically ill patients with COVID-19. The research, published in Journal of Medical Virology on January 14, 2026 [1], adds to a growing body of evidence highlighting the potential benefits of this hormone beyond its well-known role in sleep regulation.
Study Design and Methodology
Researchers at the Hospital Clínico San Carlos evaluated 335 consecutive patients admitted to the Intensive Care Unit (ICU) with severe COVID-19 between March 2020 and April 2021. [1] The study employed a quasi-experimental design, alternating between standard treatment protocols and standard treatment supplemented with high doses of oral melatonin (50, 100, or 200 milligrams daily). [1] Statistical methods were used to minimize bias in the analysis.
Key Findings: Reduced Mortality and Improved Clinical Evolution
The results demonstrated a significant association between oral melatonin administration and improved clinical evolution, as well as a substantial reduction in mortality. Specifically, mortality at 90 days was 20.8% in the groups treated with melatonin, compared to 36.1% in the groups receiving standard treatment without melatonin. [1] Miguel Sánchez García, the lead researcher and head of the Intensive Medicine Service at the Hospital Clínico San Carlos, highlighted these findings.
Safety and Tolerability
Importantly, the study found that high-dose melatonin administered over a prolonged period was well-tolerated by patients, with no adverse events directly attributable to the treatment detected. [1] This reinforces the favorable safety profile of melatonin.
Potential Applications Beyond COVID-19
Researchers suggest that these findings could pave the way for further trials investigating melatonin’s efficacy in other conditions characterized by oxidative stress and systemic inflammation. [1] These include septic shock, resuscitated cardiac arrest, and ischemic or hemorrhagic stroke, due to melatonin’s antioxidant and neuroprotective properties. [1]
About Melatonin
Melatonin is a hormone primarily known for regulating sleep-wake cycles. But, research has shown it also possesses antioxidant, anti-inflammatory, and immunomodulatory effects. [3] These properties may contribute to its observed benefits in critically ill patients.
Further research is needed to fully understand the mechanisms of action and optimal dosage of melatonin in various clinical settings.